Mechanically strong protein may be anticancer agent

Researchers from the University of Illinois at Urbana-Champaign, together with three other institutions, have found a natural agent that is showing promise blocking metastasis of cancer cells and enhancing wound healing.

Researchers from the University of Illinois at Urbana-Champaign, together with three other institutions, have found a natural agent that is showing promise blocking metastasis of cancer cells and enhancing wound healing.

The agent, called anastellin, comes from an adhesion protein called fibronectin found in the extracellular matrix surrounding cells. Crystallography, atomic-force microscopy, and advanced computer modeling let researchers sort the chemical structure and mechanical strength of fibronectin proteins that glue together cells in mammalian body tissues.

The fibronectin has special mechanical properties. "For example, when stretched mechanically, it extends in two stages, first to about one-third of its total length, then to full length, or about 10 times its initial size," says Klaus Schulten, director of theoretical and computational biophysics group at the Beckman Institute for Advanced Science and Technology.

Fibronectin modules have a two-sheet sandwich structure. But one of the sheets in a type of fibronectin called 3-1 is much stronger. "It is mainly this strong sheet that is anestellin, and it stabilizes the stretching intermediate by refusing to unravel," says Viola Vogel, professor of bioengineering and director of nanotechnology at the University of Washington, Seattle. "Cells can apply enough mechanical force to the surrounding extracellular matrix to unravel fibronectin type-three modules," she adds. "The stretching of 3-1 unmasks the buried anestellin and it appears to restrict the motion of cancer cells, in effect creating strong jail bars that hold the cancerous inmates from moving freely."